[EN] SUBSTITUTED 4,5,6,7-TETRAHYDRO-PYRAZOLO[1,5-a]PYRAZINE DERIVATIVES AND 5,6,7,8-TETRAHYDRO-4H-PYRAZOLO[1,5-a][1,4]DIAZEPINE DERIVATIVES AS ROS1 INHIBITORS<br/>[FR] DÉRIVÉS 4,5,6,7-TÉTRAHYDRO-PYRAZOLO[1,5-A]PYRAZINE SUBSTITUÉS ET DÉRIVÉS 5,6,7,8-TÉTRAHYDRO-4H-PYRAZOLO[1,5-A][1,4]DIAZÉPINE UTILISÉS COMME INHIBITEURS DE ROS1
申请人:JANSSEN PHARMACEUTICA NV
公开号:WO2015144799A1
公开(公告)日:2015-10-01
The present invention relates to substituted 4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine derivatives and 5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine derivatives of formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as ROS 1 inhibitors. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.
本发明涉及取代的4,5,6,7-四氢吡唑并[1,5-a]吡嗪衍生物和5,6,7,8-四氢-4H-吡唑并[1,5-a][1,4]二氮杂环衍生物的公式(I)中的变量具有权利要求中定义的含义。根据本发明的化合物可用作ROS 1抑制剂。本发明还涉及制备这种新化合物的方法,包含所述化合物作为活性成分的药物组合物,以及将所述化合物用作药物的用途。
Olefin metathesis catalyst bearing a chelating phosphine ligand
作者:Christina Lexer、Daniel Burtscher、Bernhard Perner、Eyal Tzur、N. Gabriel Lemcoff、Christian Slugovc
DOI:10.1016/j.jorganchem.2011.03.005
日期:2011.6
for the complex (SPY-5-34)-dichloro-(κ2(C,P)-diphenyl-(2-benzylidene)-phosphine)-(1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-imidazol-2-ylidene)-ruthenium (2) was elaborated and the title compound was tested as latent initiator in Ring Opening Metathesis Polymerization (ROMP) and as catalyst for Ring-Closing Metathesis (RCM) at elevated temperatures. While not particularly suited as latent initiator
为复合物(SPY-5-34) -二氯-一种改进的合成方法(κ 2(C,P)二苯基(2-亚苄基) -膦) - (1,3-双(2,4,6-制备了三甲基苯基)-4,5-二氢-咪唑-2-亚甲基-钌(2),并测试了标题化合物作为开环复分解聚合(ROMP)的潜在引发剂和闭环复分解(RCM)的催化剂在高温下。尽管不特别适合用作ROMP的潜在引发剂,但在典型的降冰片烯衍生物的聚合反应中,转换温度仅为42℃,但2在较高温度下的RCM中显示出令人瞩目的α,ω-二烯性能。
Deprotonation of η<sup>2</sup>(4e)-bonded alkynes as a pathway to σ,η<sup>2</sup>(3e)-prop-2-ynyl, η<sup>5</sup>-pentadienyl and η<sup>4</sup>-trans-1,3-diene substituted molybdenum complexes
作者:Carla Carfagna、Robert J. Deeth、Michael Green、Mary F. Mahon、Jacqueline M. Mclnnes、Sylvan Pellegrini、Christopher B. Woolhouse
DOI:10.1039/dt9950003975
日期:——
Li[N(SiMe3)2] to the halogenobis(alkyne) complexes [MoBr(η2-MeC2R)2(η-C5H5)](R = Me or Ph) resulted in a dehydrohalogenation reaction and formation of the σ,η2(3e)-prop-2-ynyl/η2(4e)-alkyne-substituted complexes [Moσ,η2(3e)-CH2C2R}η2(4e)-MeC2R}(η-C5H5)](R = Ph 7 or Me). The structure when R = Ph has been confirmed by a single-crystal X-ray diffraction study. The η2(4e)-bonded alkyne and σ,η2(3e)-prop-2-ynyl
的Li [N(森达的另外3)2 ]将halogenobis(炔)络合物[MoBr(η 2 -MeC 2 R)2(η-C 5 H ^ 5)](R = Me或PH)导致了脱卤化氢反应和形成的σ,η 2(3E) -丙-2-炔基/η 2(4E)-alkyne取代配合物[沫σ,η 2(3E)-CH 2 C ^ 2 R} η 2(4E )-MeC 2 R}(η-C 5 H ^ 5)](R =苯基7或Me)。通过单晶X射线衍射研究已经证实了当R = Ph时的结构。该η 2(4E)键合的炔和σ,η 2(3E) -丙-2-炔基配体位于平面基本上平行于所述η-C的5 ħ 5配位体,具有C(1)-C(2) - C(3)角和Mo–C(1),Mo–C(2)和Mo–C(3)的丙-2-炔基片段的键长为146.1(6)°,2.278(6),2.164( 5)和2.105(5)Å。所述M-σ,η的性质2 -C 3 H ^
Five‐ and Six‐Membered Cobaltocycles with C,P‐Chelating Ligands through Regiospecific Cyclometalation of Mono(2‐Substituted) Triphenylphosphane
作者:Hans‐Friedrich Klein、Robert Beck、Ulrich Flörke、Hans‐Jürgen Haupt
DOI:10.1002/ejic.200390179
日期:2003.4
P)}tris(trimethylphosphane)cobalt] (4). The molecular structure shows a trigonal-bipyramidal configuration of the cobalt atom accommodating a six-membered metallacycle. 2-(Diphenylphosphanyl)styrene replaces two trimethylphosphane ligands to give [2-(diphenylphosphanyl)styrene-(C,C-η2,P)}methylbis(trimethylphosphane)cobalt] (5), avoiding metalation. Replacement of equatorial trimethylphosphane in compounds
[CoCH3(PMe3)4]与5-(二苯基膦酰基)-1,2,3,4-四氢萘反应生成[8-(二苯基膦酰基)-1,2,3,4 -tetrahydronaphthyl-(C1,P)}tris(trimethylphosphane)cobalt] (1),包含一个五元金属环,如分子结构所示。1-(二苯基膦基)萘相应地反应,得到[8-(二苯基膦基)萘基-(C1,P)}三(三甲基膦)钴](2),2-(二苯基膦基)联苯产生邻位金属化的[2- (二苯基膦基)-3-苯基苯基-(C1,P)}三(三甲基膦)钴] (3),包含一个四元金属环。1-(二苯基膦基)-8-甲基萘在脂肪族取代基中被金属化以形成[[8-(二苯基膦基)萘-1-基]甲基-(C,P)}三(三甲基膦)钴] (4)。分子结构显示了容纳六元金属环的钴原子的三角-双锥体构型。2-(二苯基膦基)苯乙烯取代两个三甲基膦配体得到[2-(二苯基膦基)苯乙烯-(C